Interpretive Summary: Nucleotide binding oligomerization domain containing protein 1 (NOD1) is a cytosolic pattern recognition receptor that can be modulated by dietary fatty acids and phytochemicals. We found that activation of NOD1 impairs insulin signaling and glucose uptake in 3T3-L1 adipocytes. These results suggest that modulation of insulin resistance in adipocytes by dietary fatty acids is at least in part mediated by NOD1 protein.